Arsenal's Premier League title bid suffered a huge blow as West Ham earned a shock 1-0 win over the 10-man Gunners, while troubled Manchester United rallied from two goals down in a 2-2 draw at Everton on Saturday.
With leaders Liverpool not in action until Sunday's trip to Manchester City, Arsenal had a chance to close the gap in the title race with victory at the Emirates Stadium.
But Mikel Arteta's side stumbled to a first loss in 16 league games as Jarrod Bowen netted West Ham's first half winner before the Gunners had Myles Lewis-Skelly sent off after the interval.
Second-placed Arsenal, whose last top-flight defeat came at Newcastle in November, are eight points behind Liverpool, who would move a massive 11 points clear if they beat spluttering City.
After coming off the bench to score twice in the closing stages of last weekend's win at Leicester, Spain midfielder Mikel Merino started for injury-hit Arsenal as a makeshift striker.
But Arsenal's lack of cutting edge in the absence of Kai Havertz, Gabriel Jesus and Bukayo Saka was exposed when Aaron Wan-Bissaka's pin-point cross was headed in by Jarrod Bowen in the 44th minute.
There was more misery for Arsenal in the 73rd minute when Lewis-Skelly brought down Mohammed Kudus as the West Ham forward surged away on the half way line.
Lewis-Skelly was initially shown a yellow card but the defender's punishment was increased to a red after referee Craig Pawson consulted the pitchside monitor.
"We never got a grip of it. We didn't generate a threat or momentum," Arteta said.
"It is painful but this is sport. We need to feel the pain today, I think we deserve that."
At Goodison Park, United were headed for a ninth defeat in their last 13 league games as goals from Beto and Abdoulaye Doucoure put Everton two up inside 33 minutes.
Ruben Amorim's team had not mustered a shot on target until Fernandes' free-kick pulled a goal back 18 minutes from time before Manuel Ugarte's equaliser salvaged a point.
More late drama was to come as Everton were awarded a penalty deep into stoppage-time, only for referee Andy Madley to overturn his decision after a VAR review.
"We just played one half and we managed to draw the game. We didn't exist in the first half," Amorim said after his 15th-placed side's dismal run extended to just four wins in 15 league games.
Marco Asensio's first goals for Aston Villa clinched a dramatic 2-1 win against spluttering Chelsea after a costly blunder from Blues keeper Filip Jorgensen.
Enzo Fernandez's quick-fire opener put Chelsea ahead at Villa Park in a battle between top four hopefuls chasing qualification for next season's Champions League.
But Asensio, who signed on loan from Paris Saint-Germain earlier in February, netted after the interval when his goal was initially disallowed for offside before being given by VAR.
The former Real Madrid forward followed his equaliser with Villa's last-gasp winner as his shot squirmed past Jorgensen's woeful attempted save.
Chelsea have been beaten four times in their last five games in all competitions, leaving them one point adrift of the top four in sixth place.
SPURS BACK ON TRACK
Tottenham eased the pressure on boss Ange Postecoglou with a 4-1 win at third-bottom Ipswich.
Brennan Johnson put Tottenham ahead in the 18th minute with a tap-in from Son Heung-min's cutback.
Johnson was on target again eight minutes later, netting with a clinical strike from another Son assist.
Omari Hutchinson pulled one back for Ipswich in the 36th minute.
But Djed Spence's deflected 77th minute shot and Dejan Kulusevski's 84th minute finish wrapped up Tottenham's second successive victory.
Wolves moved five points clear of the relegation zone with a 1-0 win at fifth-placed Bournemouth.
Bournemouth had Illia Zabarnyi sent off late in the first half when his foul by Rayan Ait-Nouri was upgraded from a yellow to red card after VAR intervened.
Wolves took advantage in the 36th minute as Nelson Semedo's cross was missed by Dean Huijsen and Matheus Cunha steered his shot past Kepa Arrizabalaga.
Joachim Andersen's own goal put his former club Crystal Palace on course for a 2-0 win at Fulham.
Southampton slipped closer to relegation after a 4-0 defeat against south-coast rivals Brighton at St Mary's.
Joao Pedro, Georginio Rutter, Kaoru Mitoma and Jack Hinshelwood's 82nd minute effort condemned bottom of the table Southampton to a 21st defeat in 26 league games this season.